bosutinib

(redirected from Bosulif)

bosutinib

(boe-sue-ti nib) ,

Bosulif

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

Treatment of adults with chronic/accelerated/blast phase chronic myelogenous leukemia that it resistant/intolerant to previous therapies.

Action

Acts as a kinase inhibitor, specifically inhibiting the kinase that promotes CML.

Therapeutic effects

Decreased progression of CML.

Pharmacokinetics

Absorption: Absorbed following oral administration
Distribution: Unknown.
Protein Binding: 96%
Metabolism and Excretion: Mostly metabolized, mainly by the CYP3A4 enzyme system; metabolites do not have antineoplastic activity.
Half-life: 22.5 hr

Time/action profile (beneficial hematologic response)

ROUTEONSETPEAKDURATION
POwithin 8–12 wk4–6 hr (blood level)9–18 mo or longer

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Lactation: Breast feeding should be avoided; Obstetric: Pregnancy (may cause fetal harm);Concurrent use of moderate to strong CYP3A4 inbitors/inducers or P-gp inhibitors (may significantly alter drug effects).
Use Cautiously in: Hepatic impairment (dose ↓ recommended);Patients with reproductive potential (effective contraception is recommended); Pediatric: Safe and effective use in children <18 yr has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)

Ear, Eye, Nose, Throat

  • tinnitus

Respiratory

  • cough (most frequent)

Cardiovascular

  • chest pain
  • fluid retention
  • pericarditis
  • prolonged QT interval

Gastrointestinal

  • abdominal pain (most frequent)
  • ↓ appetite (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • dysgeusia
  • gastritis
  • GI bleeding
  • hepatic toxicity
  • pancreatitis

Dermatologic

  • itching (most frequent)
  • rash (most frequent)
  • acne

Fluid and Electrolyte

  • dehydration
  • hyperkalemia

Hematologic

  • anemia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)

Musculoskeletal

  • arthralgia (most frequent)
  • back pain (most frequent)
  • myalgia

Miscellaneous

  • allergic reactions including anaphlaxis
  • fever (most frequent)

Interactions

Drug-Drug interaction

Concurrent use of moderate to strong CYP3A4 inibitors including amprenavir, aprepitant, atazanavir, bocepravir, ciprofloxacin, clarithromycin, conivaptan, crizotinib, darunavir, digoxin, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, posiconazole, ritonavr, saquinavir, telaprevir, telithromcyin, verapamil and voriconazole ↑ blood levels and risk of toxicity and should be avoided.Concurrent use with CYP3A4 inducers including bosentan, carbamazepine, efavirenz, etravirine, modafinil, nafcillin, phenobarbital, phenytoin, rifabutin and rifampin may ↓ blood levels and beneficial effects and should be avoided.Proton pump inhibitors (PPIs) including esomeprazole, dexlansoprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole may ↓ blood levels and effectiveness and should be avoided, consider using short-acting antacids or histamine-H2 receptor blockers instead (these should be taken 2 hr before or 2 hr after bosutinib).May ↑ digoxin levels.Concurrent use with St. John's wort may ↓ blood levels and beneficial effects and should be avoided.Grapefruit juice may ↑ blood levels and the risk of toxicity and should be avoided.

Route/Dosage

Oral (Adults) 500 mg once daily, if complete hematologic response has not occurred by 8 wk, or complete cytologic response by 12 wk or there has been no occurrence of ≥Grade 3 adverse reactions, consider dose increase to 600 mg once daily. Dose adjustments should be made for toxicity (hematologic and non-hematologic).

Renal Impairment

Oral (Adults) CCr <30 mL/min—300 mg once daily

Hepatic Impairment

Oral (Adults) Any degree of hepatic impairment—200 mg once daily

Availability

Tablets: 100 mg, 500 mg

Nursing implications

Nursing assessment

  • Monitor for diarrhea, nausea, vomiting, and abdominal pain. For Grade 3–4 diarrhea (↑ of ≥7 stools/day over baseline/pretreatment), withhold bosutinib until recovery to Grade ≤1.
  • Assess for signs and symptoms fluid retention (swelling in hands, ankles, or feet; weight gain; shortness of breath; cough; chest pain). May manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Interrupt, reduce dose or discontinue bosutinib as necessary.
  • Monitor for signs of allergic reaction (rash, shortness of breath, respiratory tract infections, loss of appetite, headache, dizziness, back pain, joint pain, itching)
  • Lab Test Considerations: Monitor CBC weekly for first mo, then monthly thereafter. May cause thrombocytopenia, anemia, and neutropenia. If ANC <1000 x 106/L or platelets <50,000 x 106/L, withhold bosutinib until ANC ≥1000 x 106/L and platelets ≥50,000 x 106/L. Resume treatment with bosutinib at same dose if recovery occurs within 2 weeks. If blood counts remain low for >2 weeks, upon recovery, reduce dose by 100 mg and resume treatment. If cytopenia recurs, reduce dose by an additional 100 mg upon recovery and resume treatment.
    • Monitor hepatic function monthly for first 3 mo, then periodically during therapy as clinically indicated. If ↑ liver transaminases > 5 × institutional upper limit of normal (ULN) occur, withhold bosutinib until recovery to ≤2.5 × ULN and resume at 400 mg once daily thereafter. If recovery takes longer than 4 weeks, discontinue bosutinib. If transaminase ↑ ≥3 × ULN occur concurrently with bilirubin ↑ >2 × ULN and alkaline phosphatase <2 × ULN, discontinue bosutinib.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)

Implementation

  • Oral: Administer once daily with food. In patients who do not reach complete hematological response by week 8 or a complete cytogenetic response by week 12, who did not have Grade 3 or higher adverse reactions, and who are currently taking 500 mg daily, consider dose escalation to 600 mg once daily with food. Swallow tablets whole; do not crush, break or chew. Do not handle crushed or broken tablets.

Patient/Family Teaching

  • Instruct patient to take bosutinib as directed. Take missed doses as soon as remembered if within 12 hours, if longer than 12 hrs skip dose and take usual prescribed dose on the following day. Do not stop taking bosutinib without consulting health care professional. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
  • Advise patient to avoid grapefruit and grapefruit juice during therapy.
  • Advise patient to immediately report fever, jaundice (skin or the white part of your eyes turns yellow or dark “tea color” urine), symptoms of infection, fluid retention, unexpected bleeding or bruising, or blood in urine or stools occur. Advise patient to notify health care professional if diarrhea, nausea, vomiting, abdominal pain occur.
  • Inform patient to take medications that decrease stomach acid (cimetidine (Tagamet®), famotidine (Pepcid®), ranitidine (Zantac®), aluminum hydroxide/magnesium hydroxide (Maalox®), calcium carbonate (Tums®), calcium carbonate and magnesia (Rolaids®) 2 hrs before or 2 hrs after bosutinib and to avoid taking esomeprazole (Nexium®), esomeprazole strontium, dexlansoprazole (Dexilant®), lansoprazole (Prevacid®), omeprazole (Prilosec®, Vimovo®, Zegerid®), pantoprazole sodium (Protonix®), and rabeprazole (AcipHex®).
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
  • Caution female patient to use effective contraception during and for at least 30 days following discontinuation of therapy. Advise patient to avoid pregnancy and breastfeeding; notify health care professional immediately if pregnancy is suspected.

Evaluation/Desired Outcomes

  • Decreased progression of CML.
References in periodicals archive ?
M2 PHARMA-February 28, 2018-CHMP Issues Positive Opinion to Pfizer for Leukemia Therapeutics Mylotarg and Bosulif
BOSULIF (bosutinib) has been granted a positive opinion for the treatment of adults with newly diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia (Ph+ CML).
BOSULIF has been granted a positive opinion for the treatment of adults with newly diagnosed chronic phase Philadelphia chromosome-positive chronic myelogenous leukemia.
NICE concluded that the American pharma firm's drug provides effective treatment and benefits over other available treatments, such as Pfizer's (NYSE:PFE) Bosulif (bosutinib).
Since 2010, Pfizer has received 20 new drug approvals and has launched multiple products to address patients' unmet medical needs, including Ibrance, Xalkori, Bosulif, Inlyta, Eliquis, Prevnar Adult and Trumenba.
and Inlyta globally, as well as growth from Bosulif, primarily in the
to conduct a global Phase 3 clinical trial of Pfizer's BOSULIF (bosutinib).
Oncology has become one of Pfizer's biggest priorities, with the recent introductions of Xalkori for lung cancer, Inlyta for kidney cancer and Bosulif for chronic myelogenous leukemia.
Although an increasing prevalence of CML and the launch of Bosulif and Iclusig will act as driving forces of market growth, it will not be enough to compensate for erosion of Gleevec and Sprycel sales once their generic equivalents hit the market.
This decline will be driven by the launch of generic imatinib in 2015 and generic dasatinib in 2020; the increased uptake of higher-priced therapies like Bosulif and Iclusig will not be able to fully counteract the generic erosion of these two market-leading drugs.
The Committee also recommended extensions of indications for Bosulif, Feraccru, Isentress, Kineret, Lynparza and Xgeva.